Construction of homogeneous antibody-drug conjugates using site-selective protein chemistry.
Construction of homogeneous antibody-drug conjugates using site-selective protein chemistry.
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DOI：
10.1039/c6sc00170j
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发表时间：
2016-05-01
期刊：
影响因子：
8.4
通讯作者：
Bernardes GJL
中科院分区：
文献类型：
--
作者：
Akkapeddi P;Azizi SA;Freedy AM;Cal PMSD;Gois PMP;Bernardes GJL
位点选择性化学药物缀合策略的使用使得能够构建具有上级治疗功效的抗体-药物缀合物（ADC）。全身化疗是目前治疗癌症的标准护理，很少有治愈性，并且经常伴有使人衰弱的副作用。靶向给药是化疗的一种替代方案，有可能改善其低疗效和全身毒性。在靶向治疗选择中，抗体-药物缀合物（ADC）已成为最有前途的。这些结合物代表了一类新的生物药物，它们选择性地将强效细胞毒性药物递送到癌细胞，而不影响整个身体的健康组织。尽管有这样的前景，早期的异源ADC仍存在稳定性、药代动力学和疗效问题，阻碍了临床开发。抗体工程、用于药物释放的接头和化学位点选择性抗体缀合的最新进展已经导致产生均质ADC，所述均质ADC已被证明在体外和体内比其异质前体更有效。在这篇简短的综述中，我们重点讨论了药物与抗体偶联的化学位点选择性修饰策略的最新进展，以及由此产生的开发新一代同质ADC的潜力。
The use of site-selective chemical drug-conjugation strategies enables the construction of antibody–drug conjugates (ADCs) with superior therapeutic efficacy.” Systemic chemotherapy, the current standard of care for the treatment of cancer, is rarely curative and is often accompanied by debilitating side effects. Targeted drug delivery stands as an alternative to chemotherapy, with the potential to improve upon its low efficacy and systemic toxicity. Among targeted therapeutic options, antibody–drug conjugates (ADCs) have emerged as the most promising. These conjugates represent a new class of biopharmaceuticals that selectively deliver potent cytotoxic drugs to cancer cells, sparing healthy tissue throughout the body. Despite this promise, early heterogenous ADCs suffered from stability, pharmacokinetic, and efficacy issues that hindered clinical development. Recent advances in antibody engineering, linkers for drug-release, and chemical site-selective antibody conjugation have led to the creation of homogenous ADCs that have proven to be more efficacious than their heterogeneous predecessors both in vitro and in vivo. In this minireview, we focus on and discuss recent advances in chemical site-selective modification strategies for the conjugation of drugs to antibodies and the resulting potential for the development of a new generation of homogenous ADCs.
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可光透明的DNA条形码 - 抗体结合物可以在单个细胞中敏感和多重蛋白质分析。
影响因子：
15
作者：
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通讯作者：
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4.7
作者：
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影响因子：
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通讯作者：
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影响因子：
15
作者：
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影响因子：
3.2
作者：
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通讯作者：
Barbas, Carlos F., III